We have made good progress in defining the sequences rules governing frameshifting to both left and right at "hungry" codons where bacterial ribosomes pause for lack of cognate aminoacyl-tRNA. Our specific aims during the next grant period are as follows. l) We will extend the definition of sequences rules for shifting in both directions, with a view toward testing specific mechanisms. 2) We will test the independence of frameshift events, with a view toward determining whether such events are concentrated in a minority of shift- or error-prone ribosomes. 3) We will analyze the possible involvement of downstream secondary structure in promoting frameshifting in both directions; and the interrelationship between effects of secondary structures and effects of ribosome pausing at hungry codons, or at codons calling for rare tRNA species. 4) We have developed an E. coli model system for investigating leftward shifting on the HIV-1 shifty sequence. We will pay particular attention to aims (1) and (3) above as applied to this sequence. We will also analyze the sequence rules and mechanism by which shifting on this sequence responds to two stimuli we have recently discovered: growth rate in different media, and the action of aminoglycoside antibiotics.